rs9321939

Variant names:

• chr6-143733635-T-C
• rs9321939
• NM_001100164.2:c.215-15350T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001100164.2(PHACTR2):​c.215-15350T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,094 control chromosomes in the GnomAD database, including 2,716 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2716 hom., cov: 32)
• Consequence: PHACTR2 NM_001100164.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.462
• Publications: 0 publications found

Genes affected

PHACTR2 (HGNC:20956): (phosphatase and actin regulator 2) Predicted to enable actin binding activity. Predicted to be involved in actin cytoskeleton organization. Predicted to be located in plasma membrane and platelet alpha granule membrane. Implicated in Parkinson's disease and multiple sclerosis. Biomarker of Alzheimer's disease. [provided by Alliance of Genome Resources, Apr 2022]

PHACTR2 Gene-Disease associations (from GenCC):

• dilated cardiomyopathy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100164.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHACTR2	NM_001100164.2	MANE Select	c.215-15350T>C		intron	N/A	NP_001093634.1	O75167-4
	PHACTR2	NM_014721.3		c.182-15350T>C		intron	N/A	NP_055536.2	O75167-1
	PHACTR2	NM_001394736.1		c.386-15350T>C		intron	N/A	NP_001381665.1	J3KP75

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHACTR2	ENST00000440869.7	TSL:2 MANE Select	c.215-15350T>C		intron	N/A	ENSP00000417038.2	O75167-4
	PHACTR2	ENST00000427704.6	TSL:1	c.182-15350T>C		intron	N/A	ENSP00000391763.2	O75167-1
	PHACTR2	ENST00000367582.7	TSL:1	c.215-15350T>C		intron	N/A	ENSP00000356554.3	O75167-2

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25775 AN: 151976 Hom.: 2718 Cov.: 32

Gnomad AFR AF: 0.0499

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.0949

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.155

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.169 AC: 25779 AN: 152094 Hom.: 2716 Cov.: 32 AF XY: 0.167 AC XY: 12441 AN XY: 74346

African (AFR) AF: 0.0498 AC: 2068 AN: 41500

American (AMR) AF: 0.124 AC: 1895 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 744 AN: 3466

East Asian (EAS) AF: 0.0957 AC: 495 AN: 5174

South Asian (SAS) AF: 0.253 AC: 1219 AN: 4814

European-Finnish (FIN) AF: 0.206 AC: 2180 AN: 10568

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16614 AN: 67976

Other (OTH) AF: 0.156 AC: 329 AN: 2112

Alfa AF: 0.187 Hom.: 1396

Bravo AF: 0.153

Asia WGS AF: 0.172 AC: 597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	11
DANN	Benign	0.72
PhyloP100		0.46
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9321939; hg19: chr6-144054772; COSMIC: COSV59852488;